“TheCulprit of Aging”
By Don C. Reed
Dr.Helen Blau of Stanford is attempting something seemingly impossible: to treat aging as a disease; to lessen the devastation of old age; to recover strength,muscle mass, and endurance—for people already old.
Accordingto Dr. Blau, a typical person past 50 will lose 10-15% of their strength everydecade. But is this inevitable?
Notif a molecule called PGE2 turns out to be helpful.
WhenDr. Blau gave PGE2 to old mice, it stimulated muscle stem cells and restored strength, muscle massand endurance to their aged limbs. They ran faster and longer on the treadmill.
Shealso discovered a protein that breaks down PGE2, so it will not work. Shecalled the negative protein a gerozyme, an aging associated enzyme, also knownas15-PGDH,a prostaglandin degrading enzyme.
Thegerozyme accumulates in muscle tissue as we age. Because the gerozyme ispresent in relatively higher amounts in the elderly, the availability of PGE2decreases, which is problematic for muscle regeneration.
So,the “hero” of aging could be PGE2 (prostaglandin), and the “villain” is thegerozyme 15-PDGH (hydroxyprostaglandin dehydrogenase).
PGE2could make muscles more powerful; 15 PDGH could wither the limbs.
Presently,Dr. Blau is working on a number of projects related to this finding. One usesPGE2 to strengthen the diaphragm, the muscle your body uses to breathe, to helpCOVID-19 survivors or pneumonia victims regain muscle strength lost from beingon a ventilator.
Asecond current focus is on the neuromuscular junction- the contact between thenerve, which transmits the signal directing a muscle to move. Her group’spreliminary data suggests that elevating PGE2 levels could help restore thesejunctions and re-establish these key connections that are lost after injury orwith aging.
Thereis also the possibility of alleviating sarcopenia, a systemic weakening of themuscles, afflicting about 15% of the population aged 60 yr and 30% aged 80yr,costing America hundreds of billions of dollars a year in health care. This age-related muscle loss negativelyimpacts the quality of life and often leads to institutionalization due to lackof mobility and loss of autonomy.
Andwhat about sphincters? Rejuvenated muscles might include an aged urinarysphincter and aid in its recovery of strength.
Everythingwe do depends on muscle—if it wastes away, so do we.
Canthe substance be safe for human use?
“Ingel form, PGE2 is already being used in a localized treatment to induce labor duringchildbirth. says Blau.
Ihad a brief conversation with Dr. Blau recently:
Q:In your work with COVID, is the primary potential benefit a repair of weaknessin the muscle wall of the diaphragm?
A:Yes, but there is more to it than that. When a person comes off a ventilator,the muscles have grown weaker through disuse. Depending on how long he/she wason the ventilator, there is a real possibility the diaphragm will simplycollapse. This can be a potential risk of death. It’s a big problem with COVID,because some people have had to be ventilated for days during which time thediaphragm muscles weaken substantially. We hope that we can use PGE2 tostrengthen diaphragm muscles to help mitigate the weakness that comes frombeing on a ventilator. This would also help increase the supply ofventilators by decreasing how long people are kept on them.
Q:Might there be a use for it in the battle against Spinal Muscular Atrophy(SMA), that deadly killer of children?
A:Yes. Any condition with muscle wasting and loss of strength mightbenefit. There are some promising therapeutics aimed at treating the neuronloss in SMA, but not many for muscles. Neuronal and muscle function gohand in hand.
Q:Might your therapy benefit people with Sarcopenia—overall aging-associated weakness?
A:Yes. Sarcopenia affects 15% of the population over 60. One very real fear isthat the body becomes so weak with Sarcopenia and its debilitating loss ofstrength that the patient can’t get out of a chair and may fall and break bonesin the attempt.
Ourgoal is two pronged ---(1) localized muscle strengthening, eg: for urinaryincontinence or carpal tunnel syndrome and (2) global muscle strengthening toincrease size and strength of muscles throughout the entire body.
Q:Would it be correct to say that your overall goal is to augment the function ofatrophied muscle-- restoring power with increased muscle mass?
A:Yes. For instance, Duchenne muscular dystrophy patients experience severemuscle wasting. We could likely mitigate some of that loss of skeletalmuscle strength. We do not yet know the effects of PGE2 on the heart; weneed to know that, because it is heart muscle failure from which patients die.
Q:Would there be military applications?
A:Yes, absolutely. Wounded soldiers are often bedridden for extendedperiods of time. It is vital that they recover strength and mobility as soon aspossible, to lessen the possibility of permanent damage.
Q:You have a biotech company: Myoforte Therapeutics; what does that mean?
A:It’s a hybrid. Myo is a prefix that indicates “muscle” (Greek origin), andforte is from the Latin and signifies “strength”. Our company merged with Epirium which isfiling for an IND to start clinical trials.
Itis to be hoped that Dr. Blau’s work may help patients maintain strength andphysical independence— combatting the one disease to which we are all subject:old age.